Immune Response to Infection Flashcards
What are the key mediators of immunity?
Phagocytes and lymphocytes are key mediators of immunity
What is the role of phagocytes?
internalize pathogens and degrade them
What do B cells do?
Make antibodies - that are also effective against extracellular pathogens
What do T helper cells do?
Coordinate the immune response by direct cell-cell interactions and the release of cytokines
What are the two essential features of the adaptive immune system?
Specificity and memory
Which immune response is able to mount a more effective response on second and subsequent encounter with a particular antigen?
The adaptive immune response
Which immune response does not alter on repeated exposure to an infectious agent?
Innate immune response
What are antigens?
Molecules that are recognised by receptors on lymphocytes
How do B and T cells differ in their interactions with antigen molecules?
B cells usually recognise intact antigen molecules, whereas T cells generally recognise antigen fragments that are displayed on the surface of the bodys own cells - in MHC
what are the two phases of the immune response?
Antigen recognition & antigen eradication
Which T Helper cells release IFN-Gamma?
Th1
Which interleukins are released by Th2?
IL-4/IL-5/IL-13
Which interleukins are released by Th17?
IL-17/IL-22
What is the principal function of the immune system?
To distinguish self from non-self
What are some examples of extracellular pathogens?
Staphylococcus, Streptococcus, Candida, microbiota, worms
What are some examples of surface adherant pathogens?
Enteropathogenic and enterohaemorrhagic E.Coli
What two areas can intracellular pathogens occupy?
Vacuole or cytoplasm
What are some examples of cytosolic intracellular pathogens?
Listeria, Burkholderia and Mycobacterium
What are some examples of intracellular vacuolar pathogens?
Salmonella, Chlamydia, Legionella Coxiella, Plasmodium
How does an immune response to infection start?
Tissue damage
Detection of microbes
What enables intercellular communication once tissue damage or microbes have been detected by the cells?
Interleukins and Chemokines - help prime the adaptive immune response
How does an immune response end?
- Clears pathogen
- Stops inflammatory cytokine production
- Repair tissue damage
What type of receptors does the innate immune system involve?
Germ line encoded receptors
What are the physical barriers that are included in the innate immune system?
Skin, mucous, epithelial cells
What does the humoral innate immune system comprise of?
Complement, Lectins, Pentraxins and antimicrobial peptides
What are the components of the cellular innate immune response?
Neutrophils, Macrophages, DC’s and NK cells
What are the components of the humoral adaptive immune system?
Antibodies and complement
What are the components of the cellular adaptive immune response?
T Killer Cells, T Helper Cells, T reg Cells, B cells and Plasma Cells
Which receptors does the adaptive immunity use?
Variable receptors that mature over time due to DNA recombination
What are PAMPs?
Pathogen Associated Molecular Patterns - These are features shared by classes of microbes that are recognised by identical toll like receptors
What is the difference in the receptors between the innate and adaptive immune system?
Innate = <100 receptors
Adaptive - two types of receptors with many variations of each due to VDJ gene rearrangement
How is the adaptive immune system able to recognise such a wide range of antigens?
Gene recombination encoding for a wide range of receptors
Describe the general principle of the sequence of molecular and cellular events which occur in the immune system?
- Microbial molecules are detected (through ligands or activities)
- Detected by Naive Host cells
- Gene expression of Host cell changes, to produce interleukins, chemokines and interferons which provide intercellular communication
- Therefore, neighbouring cells then communicate to cells that they should prepare to fight the pathogen = activated host cells
How does a resting cell become an activated cell?
Interleukins, chemokines and interferons act on the resting cell in an autocrine manner to become specialised
What is the central mechanism by which a resting cell is converted into a specialised cell which is able to better respond to pathogens
Gene expression changes
What are the first responders to the site of injury?
Neutrophils
What are the second responders to the site of injury?
Macrophages
How do naive neutrophils and macrophages become activated?
induced by cytokines or microbes
What problems can arise from the uncontrolled activities of phagocytes?
Granulomas
Excessive Inflammation
Tissue Damage
How do neutrophils recognise which class of pathogen has invaded?
Through molecules which are common to that specific pathogen class
What is a major pattern recognition molecule in E.Coli?
Lipopolysaccharide - LPS
What is the difference in phagocyte response between dead and alive pathogens?
Live = brings about a dramatic change in gene expression, leads to release of cytokines and transcription of antimicrobial and metabolic genes
Dead = no immune response, try to resolve inflammation
Which surface molecule are unique to fungi and helps phagocytes to recognise that the pathogen is in fact fungi?
Beta-glucan in the polysaccharide cell wall
What molecules do fungi signal through to stimulate an immune response?
STK - Serine Tyrosine Kinases
What is the pro-inflammatory response generated from fungi?
- Pro-inflammatory cytokines
- Antimicrobial genes
- Metabolic genes
- Immunomodulatory genes
What is the pro-inflammatory response generated from viruses?
IFN Production
Pro-inflammatory cytokines
Anti-viral genes
Immunomodulatory genes
Describe with the use of Salmonella how macrophages becomes activated and kill phagocytosed bacteria?
- Bacteria is within the macrophage
- Macrophages releases cytokines - particularly IL-12
- These act on lymphocytes to cause the lymphocyte to start producing IFN-gamma
- Causes the macrophage to change its gene expression and start producing a whole host of genes that are directly toxic to the bacteria
Which two immune cells undergo cross talk during macrophage activation?
Macrophages and Lymphocytes
What two things result in the production of interferons?
Detection of virus or gram negative bacteria
What are four types of anti-viral genes which Interferons stimulate the synthesis of?
- Nucleases
- Inhibitors of viral entry/exit
- Inhibitors of viral uncoating and replication
- Inhibitors of protein translation
What are the three immunomodulatory roles of interferon?
Enhance T cell responses
Anti-inflammatory actions
Tissue Repair
How are virally-infected cells killed?
The actions of cytotoxic T lymphocytes or NK Cells
What is the killing of virally infected cells by cytotoxic T lymphocytes and Natural Killer Cells dependant on?
Contact with the cell
How does an NK cell recognise a virus-infected cell?
Through the down regulation of MHC on the surface
What is nitric oxide?
A radical which is highly toxic to intracellular pathogens
Which of the three types of interferon promote antiviral responses?
Type I and III
Which type of interferon promotes antibacterial immunity?
Type II
Why are dendritic cells better at responding to viral infections than macrophages?
Dendritic cells can produce a lot of type 1 interferon during infection
How do dendritic cells present antigens to T cells?
Through MHC molecules
What happens when a naive t cell binds MHC with antigen from a dendritic cell?
This coupled with the release of cytokines causes the T cell to release more cytokines which act in an autocrine manner and help the T cel differentiate into specific T cells to fight that particular pathogen
Which cytokines convert the naive T cell into one that fights fungi and extracellular bacteria?
Th17 - needs IL-17 and IL22
Which cytokines convert the naive T cell into one that fights intracellular pathogens?
IFN-Gamma
Which cytokines convert the naive T cell into one that fights helminths?
IL-4
IL-5
IL-13
How do T cells help B cells produce Antibodies?
- APC’s are activated by infection and cytokines
- They present antigen to T cells - T cells activated by cognate MHC and foreign peptide recognition
- B cells become licensed for antibody production against the antigen being present on the BCR
- Antibodies are produced
What are the two components of an antibody-mediated enhanced anti-microbial response?
- Phagocytosis (opsonisation)
- complement activation
what are the four broad roles of T cells?
- Phagocyte activation
- Direct killing of infected cells
- B cells activation
- Innate lymphoid cells
Which cytokines do eosinophils produce? And what T cell do these result in?
makes Th2
IL-4, IL-5 and IL-13
What is the primary event which occurs in the innate immune response?
The sequential change from “Resting” Phagocytes to “Activated” phagocytes which is driven by gene expression changes due to different combination of cytokines being released
What is the timing of the innate immune response?
0-12 hours post infection
Which immune cells are present in the first 12 hours following infection?
Mast cells, Dendritic cells, NK Cells, Phagocytes, Epithelial barriers, complement
What results in the production of B and T cells after a few days following infection?
Antigen presentation to T Lymphocytes
How many weeks after exposure to antigen X does the peak of the primary anti-X response occur?
1 weeK
Describe the secondary immune response in relation to the primary immune response?
It is much faster and greater in effect
At what age does thymic declines?
halts at a low level at about 30
What happens to the percentage of T cells in the blood that are Naive T cells as you age?
Decreases
What happens to the percentage of T cells in the blood that are Memory T cells as you age?
Increases
How do we fight infection?
Innate and adaptive immunity
What is the difference between the adaptive and innate immune response?
What can be different about the adaptive and innate immunity?
Differences in
* Timing of the response
* Cell types
* Receptors & ligands
* Cytokines & chemokines
* Molecular effector machineries
- Both arms of the immune system together provide sterilising immunity and long- term memory
What are the pathogen niches during infection?
Extracellular
Surface adherent
Intracellular but cytosolic
Intracellular but vacuolar
How does an immune response to infection start?
Tissue damage
Detection of pathogens
What are the first responder cells?
neutrophils and macrophages
What are the difference in the pathogen specific responses by phagocytes depending on the pathogen?
How do T and B cells enhance antimicrobial immunity?
What are examples of genetic and acquired immunodeficiencies?
